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Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial
Jie-Eun Lee, Seung Hee Yu, Sung Rae Kim, Kyu Jeung Ahn, Kee-Ho Song, In-Kyu Lee, Ho-Sang Shon, In Joo Kim, Soo Lim, Doo-Man Kim, Choon Hee Chung, Won-Young Lee, Soon Hee Lee, Dong Joon Kim, Sung-Rae Cho, Chang Hee Jung, Hyun Jeong Jeon, Seung-Hwan Lee, Keun-Young Park, Sang Youl Rhee, Sin Gon Kim, Seok O Park, Dae Jung Kim, Byung Joon Kim, Sang Ah Lee, Yong-Hyun Kim, Kyung-Soo Kim, Ji A Seo, Il Seong Nam-Goong, Chang Won Lee, Duk Kyu Kim, Sang Wook Kim, Chung Gu Cho, Jung Han Kim, Yeo-Joo Kim, Jae-Myung Yoo, Kyung Wan Min, Moon-Kyu Lee
Diabetes Metab J. 2024;48(4):730-739.   Published online May 20, 2024
DOI: https://doi.org/10.4093/dmj.2023.0077
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AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Background
It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia.
Methods
This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment.
Results
After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events.
Conclusion
The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

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Citations to this article as recorded by  
  • Real-world safety evaluation of atorvastatin: insights from the US FDA adverse event reporting system (FAERS)
    Hongbing Wan, Xiuxiu Xu, Dasong Yi, Kexin Shuai
    Expert Opinion on Drug Safety.2024; : 1.     CrossRef
Clinical Characteristics of Type 2 Diabetes Patients according to Family History of Diabetes
Seung Uk Jeong, Dong Gu Kang, Dae Ho Lee, Kang Woo Lee, Dong-Mee Lim, Byung Joon Kim, Keun-Yong Park, Hyoun-Jung Chin, Gwanpyo Koh
Korean Diabetes J. 2010;34(4):222-228.   Published online August 31, 2010
DOI: https://doi.org/10.4093/kdj.2010.34.4.222
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  • 17 Crossref
AbstractAbstract PDFPubReader   
Background

Type 2 diabetes mellitus (T2DM) has a strong genetic component, and its prevalence is notably increased in the family members of T2DM patients. However, there are few studies about the family history of T2DM. We carried out this study to assess the influences of family history on clinical characteristics in T2DM patients.

Methods

This is a cross-sectional study involving 651 T2DM patients. Patient history and physical examination were performed and fasting blood was taken. If any first degree relative was diabetic, a family history of diabetes was considered to exist.

Results

Among the total 621 patients, 38.4% had a family history of diabetes. Patients with a family history had a younger age, higher weight, younger age at diagnosis and higher triglyceride level than did those without a family history. Dyslipidemia medication and metabolic syndrome were more prevalent in familial diabetes. Sex, blood pressure, previous treatment for diabetes, HbA1c, C-peptide, total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol were not different between familial and non-familial diabetes. Upon multiple linear regression analysis, the family history of diabetes remained significantly associated with serum triglyceride level.

Conclusion

In T2DM patients with a family history of diabetes, the disease tended to develop earlier. Metabolic syndrome and cardiovascular risk factors are more prevalent in familial T2DM than they were in non-familial T2DM. These results support the necessity of earlier screening for diabetes in family members of T2DM patients and more active prevention against cardiovascular disease in T2DM patients with a family history.

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  • COVID-19-Induced Diabetes Mellitus: Comprehensive Cellular and Molecular Mechanistic Insights
    Praise Tatenda Nhau, Mlindeli Gamede, Ntethelelo Sibiya
    Pathophysiology.2024; 31(2): 197.     CrossRef
  • Positive parental history of diabetes is associated with early diagnosis, better dietary compliance, and glycemic control among type 2 diabetes patients in southern Sri Lanka
    Warsha De Zoysa, Thilak Priyantha Weerarathna, Keddagoda Gamage Piyumi Wasana, Miyuru Kavinda Weerarathna, Vidarsha Senadeera
    Diabetology & Metabolic Syndrome.2024;[Epub]     CrossRef
  • Effects of Propolis Consumption on Glycemic Indices and Liver Enzymes in Adults: A Grading of Recommendations Assessment, Development, and Valuation-assessed Systematic Review and Dose-Response Meta-analysis
    Shaghayegh Adeli, Mahsa Maroofi, Fatemeh Pourteymour Fard Tabrizi, Beitullah Alipour, Marzieh Heidari, Mahdi Vajdi, Mahdieh Abbasalizad-Farhangi
    Clinical Therapeutics.2024; 46(9): e6.     CrossRef
  • Evolutionary algorithm for the optimization of meal intake and insulin administration in patients with type 2 diabetes
    Eva Gonzalez-Flo, Elaheh Kheirabadi, Carlos Rodriguez-Caso, Javier Macía
    Frontiers in Physiology.2023;[Epub]     CrossRef
  • Role of Cytokines (IL-17 and IL-33), FGF-18, and WNT-5 in the Pathogenesis of Patients with Established Type II Diabetes
    Przha Mohammed, Kawa Amin
    Journal of Zankoy Sulaimani - Part A.2023; 25(2): 11.     CrossRef
  • Cellular Chitchatting: Exploring the Role of Exosomes as Cardiovascular Risk Factors
    Giulia Germena, Laura Cecilia Zelarayán, Rabea Hinkel
    Frontiers in Cell and Developmental Biology.2022;[Epub]     CrossRef
  • Combined associations of family history and self-management with age at diagnosis and cardiometabolic risk in 86,931 patients with type 2 diabetes: Joint Asia Diabetes Evaluation (JADE) Register from 11 countries
    Johnny T. K. Cheung, Eric Lau, Cyrus C. T. Tsui, Edmond L. N. Siu, Naomi K. W. Tse, Nicole Y. L. Hui, Ronald C. W. Ma, Alice P. S. Kong, Amy Fu, Vanessa Lau, Weiping Jia, Wayne H. H. Sheu, Leorino Sobrepena, K. H. Yoon, Alexander T. B. Tan, Yook-Chin Chia
    BMC Medicine.2022;[Epub]     CrossRef
  • Capsaicin, its clinical significance in patients with painful diabetic neuropathy
    Phiwayinkosi V. Dludla, Bongani B. Nkambule, Ilenia Cirilli, Fabio Marcheggiani, Sihle E. Mabhida, Khanyisani Ziqubu, Yonela Ntamo, Babalwa Jack, Tawanda M. Nyambuya, Sidney Hanser, Sithandiwe E. Mazibuko-Mbeje
    Biomedicine & Pharmacotherapy.2022; 153: 113439.     CrossRef
  • Safety profile of sodium glucose co-transporter 2 (SGLT2) inhibitors: A brief summary
    Annamaria Mascolo, Raffaella Di Napoli, Nunzia Balzano, Donato Cappetta, Konrad Urbanek, Antonella De Angelis, Lucia Scisciola, Irene Di Meo, Maria Giuseppa Sullo, Concetta Rafaniello, Liberata Sportiello
    Frontiers in Cardiovascular Medicine.2022;[Epub]     CrossRef
  • Impact of triglycerides and waist circumference on insulin resistance and β-cell function in non-diabetic first-degree relatives of type 2 diabetes
    Fahd Ahmed, Molham AL-Habori, Ebtesam Al-Zabedi, Riyadh Saif-Ali
    BMC Endocrine Disorders.2021;[Epub]     CrossRef
  • Orientin Improves Substrate Utilization and the Expression of Major Genes Involved in Insulin Signaling and Energy Regulation in Cultured Insulin-Resistant Liver Cells
    Sithandiwe E. Mazibuko-Mbeje, Sinenhlanhla X. H. Mthembu, Andani Tshiitamune, Ndivhuwo Muvhulawa, Fikile T. Mthiyane, Khanyisani Ziqubu, Christo J. F. Muller, Phiwayinkosi V. Dludla
    Molecules.2021; 26(20): 6154.     CrossRef
  • Identification of Pre-Diabetic Biomarkers in the Progression of Diabetes Mellitus
    Jae-Ho Lee, Do-Young Kim, Rubee Pantha, Eun-Ho Lee, Jae-Hoon Bae, Eugene Han, Dae-Kyu Song, Taeg Kyu Kwon, Seung-Soon Im
    Biomedicines.2021; 10(1): 72.     CrossRef
  • Shared (epi)genomic background connecting neurodegenerative diseases and type 2 diabetes
    Valerio Caputo, Andrea Termine, Claudia Strafella, Emiliano Giardina, Raffaella Cascella
    World Journal of Diabetes.2020; 11(5): 155.     CrossRef
  • Family history of diabetes in both parents is strongly associated with impaired residual β‐cell function in Japanese type 2 diabetes patients
    Minoru Iwata, Yutaka Kamura, Hisae Honoki, Kaori Kobayashi, Manabu Ishiki, Kunimasa Yagi, Yasuo Fukushima, Atsuko Takano, Hiromi Kato, Shihou Murakami, Kiyohiro Higuchi, Chikaaki Kobashi, Kazuhito Fukuda, Yukiko Koshimizu, Kazuyuki Tobe
    Journal of Diabetes Investigation.2020; 11(3): 564.     CrossRef
  • The relationship between age of onset and risk factors including family history and life style in Korean population with type 2 diabetes mellitus
    Jin-Won Noh, Jin Hee Jung, Jeong Eun Park, Jung Hwa Lee, Kang Hee Sim, Jumin Park, Min Hee Kim, Ki-Bong Yoo
    Journal of Physical Therapy Science.2018; 30(2): 201.     CrossRef
  • Clinical Characteristics of Subjects with Sulfonylurea-Dependent Type 2 Diabetes
    Se Hee Min, Soo Heon Kwak, Young Min Cho, Kyong Soo Park, Hye Seung Jung
    Endocrinology and Metabolism.2015; 30(4): 509.     CrossRef
  • Nutritional Assessment of Type II Diabetic Patients
    El-Sayed H. Bakr
    Pakistan Journal of Nutrition.2015; 14(6): 308.     CrossRef
Review
Stimulation of Glucagon Like Peptide-1 Secretion in Enteroendocrine L cells.
Byung Joon Kim
Korean Diabetes J. 2009;33(6):458-463.   Published online December 1, 2009
DOI: https://doi.org/10.4093/kdj.2009.33.6.458
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  • 2 Crossref
AbstractAbstract PDF
GLP-1 (glucagon like peptide-1) is new anti-diabetic drug with a number of beneficial effects. It stimulates glucose dependant insulin secretion and restoration of beta cell mass through enhancement of islet mass. However, it is easily inactivated after being secreted from enteroendocrine L cells. Recent trial to increased GLP-1 is to directly stimulate L cells through its receptor located in the surface of L cell. Taste receptor in the apical surface of L cell is activated by various tastants contained in the food. Tongue perceives taste sense through the heterotrimeric G-protein (alpha-gustducin) and its downstream signaling cascades. Same taste receptors are also expressed in enteroendocrine cells. In duodenal L cell, alpha-gustducin was detected by immunofluorescence stainig at the luminal projections of enteroendocrine cells. And several other taste signaling elements were also found in L cells. Ingestion of sweet or bitter compounds revealed stimulation of GLP-1 secretion and the regulation of plasma insulin and glucose. In this review, I will briefly introduce the possibilities to stimulate GLP-1 secretion though the membrane receptor in enteroendocrine cell. And it will be the good candidate to develop the treatment modality for obesity, diabetes and abnormal gut motility.

Citations

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  • Repression of sterol regulatory element-binding protein 1-c is involved in the protective effects of exendin-4 in pancreatic β-cell line
    Seok-Woo Hong, Jinmi Lee, Se Eun Park, Eun-Jung Rhee, Cheol-Young Park, Ki-Won Oh, Sung-Woo Park, Won-Young Lee
    Molecular and Cellular Endocrinology.2012; 362(1-2): 242.     CrossRef
  • Exendin-4 Protects Oxidative Stress-Induced β-Cell Apoptosis through Reduced JNK and GSK3β Activity
    Ju-Young Kim, Dong-Mee Lim, Chan Il Moon, Kyung-Jin Jo, Seong-Kyu Lee, Haing-Woon Baik, Ki-Ho Lee, Kang-Woo Lee, Keun-Young Park, Byung-Joon Kim
    Journal of Korean Medical Science.2010; 25(11): 1626.     CrossRef
Letter
Letter: Risk Factors for Early Development of Macrovascular Complications in Korean Type 2 Diabetes (Korean Diabetes J 33(2):134-142, 2009).
Byung Joon Kim
Korean Diabetes J. 2009;33(3):257-258.   Published online June 1, 2009
DOI: https://doi.org/10.4093/kdj.2009.33.3.257
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AbstractAbstract PDF
No abstract available.
Case Report
Maintenance of Insulin Therapy by Desensitization in Insulin Allergy Patient.
Jun Hwa Hong, Ji Hye Lee, Jong Ho Shin, Dong Pil Kim, Bong Suk Ko, Byung Joon Kim, Hyun Jin Kim, Kang Seo Park
Korean Diabetes J. 2008;32(6):529-531.   Published online December 1, 2008
DOI: https://doi.org/10.4093/kdj.2008.32.6.529
  • 2,695 View
  • 34 Download
  • 4 Crossref
AbstractAbstract PDF
Allergic reaction to human insulin is uncommon. But they can cause mild to severe symptoms such as dyspnea, hypotensive shock, etc. Here we report the case of a patient with type 2 diabetes and insulin allergy successfully managed with desensitization. A 60-year-old man with insulin allergy was transferred. He had poorly controlled type 2 diabetes (fasting blood glucose 230 mg/dL). He developed itching sense and erythema at the injection sites of human insulin in a few minutes. And serum IgE level was elevated to 1618.0 IU/mL. The insulin was changed to other preparations, including short and long-acting insulin analogues, with similar responses. He was commenced on twice a day injection protocol in addition to his oral hypoglycemic agents, and achieved fair control (fasting blood glucose 100 mg/dL) on 24 units of Novomix Flex Pen per day, with little or no skin or systemic reaction. This is the case report of insulin allergy in type 2 diabetes being successfully managed by desensitization.

Citations

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  • Allergic reaction to recombinant human insulin
    Seong Jin Choi, Min Kwan Kwon, Moon Park, Soo Ya Bae, Hyun Ho Oh, Jong Ho Lee, Ji In Moon, Chan Sun Park, Jong Chul Won, Kyung Soo Ko, Byoung Doo Rhee, Jung Min Kim
    Allergy, Asthma & Respiratory Disease.2015; 3(4): 302.     CrossRef
  • Two Cases of Allergy to Insulin in Gestational Diabetes
    Gi Jun Kim, Shin Bum Kim, Seong Il Jo, Jin Kyeong Shin, Hee Sun Kwon, Heekyung Jeong, Jang Won Son, Seong Su Lee, Sung Rae Kim, Byung Kee Kim, Soon Jib Yoo
    Endocrinology and Metabolism.2015; 30(3): 402.     CrossRef
  • Successful Management of Insulin Allergy and Autoimmune Polyendocrine Syndrome Type 4 with Desensitization Therapy and Glucocorticoid Treatment: A Case Report and Review of the Literature
    Joselyn Rojas, Marjorie Villalobos, María Sofía Martínez, Mervin Chávez-Castillo, Wheeler Torres, José Carlos Mejías, Edgar Miquilena, Valmore Bermúdez
    Case Reports in Immunology.2014; 2014: 1.     CrossRef
  • Clinical applications of drug desensitization in the Asia-Pacific region
    Bernard Yu-Hor Thong
    Asia Pacific Allergy.2011; 1(1): 2.     CrossRef
Original Article
Protective Effects of Glucagon Like Peptide-1 on HIT-T15 beta Cell Apoptosis via ER Stress Induced by 2-deoxy-D-glucose.
Ju Young Kim, Seong Kyu Lee, Haing Woon Baik, Ki Ho Lee, Hyun Jin Kim, Kang Seo Park, Byung Joon Kim
Korean Diabetes J. 2008;32(6):477-487.   Published online December 1, 2008
DOI: https://doi.org/10.4093/kdj.2008.32.6.477
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  • 3 Crossref
AbstractAbstract PDF
BACKGROUND
The characteristic feature of pancreatic beta cells is highly developed endoplasmic reticulum (ER) due to a heavy engagement in insulin secretion. The ER serves several important function, including post-translational modification, folding, and assembly of newly synthesized secretory proteins, and its proper function is essential to cell survival. Various stress conditions can interfere with ER function. Pancreatic beta cells may be particularly vulnerable to ER stress that causes to impair insulin biosynthesis and beta cell survival through apoptosis. Glucagon like peptide-1 (GLP-1) is a new drug for treatment of type 2 diabetes and has effects on stimulation of insulin secretion and beta cell preservation. Also, it may have an antiapoptotic effect on beta cells, but detailed mechanisms are not proven. Therefore, we investigated the protective mechanism of GLP-1 in beta cells through ER stress response induced by 2-deoxy-D-glucose (2DG). METHODS: For induction of the ER stress, HIT-T15 cells (hamster beta cell line) were treated with 2DG (10 mM). Apoptosis was evaluated with MTT assay, hoechst 33342 staining and Annexin/PI flow cytometry. Expression of ER stress-related molecules was determined by real-time PCR or western blot. For blocking ER stress, we pretreated HIT-T15 cells with exendin-4 (Ex-4; GLP-1 receptor agonist) for 1 hour before stress induction. RESULTS: After induction with ER stress (2DG), beta cells were lost by apoptosis. We found that Ex-4 had a protective effect through ER stress related molecules (GRP78, GRP94, XBP-1, eIF2alpha, CHOP) modulation. Also, Ex-4 recovered the expression of insulin2 mRNA in beta cells. CONCLUSION: These results suggest that GLP-1 may protect beta cells apoptosis through ER stress modulation.

Citations

Citations to this article as recorded by  
  • Exendin-4 Protects Against Sulfonylurea-Induced β-Cell Apoptosis
    Ju-Young Kim, Dong-Mee Lim, Hyung-Seo Park, Chan-Il Moon, Kyung-Jin Choi, Seong-Kyu Lee, Haing-Woon Baik, Keun-Young Park, Byung-Joon Kim
    Journal of Pharmacological Sciences.2012; 118(1): 65.     CrossRef
  • GLP-1 Can Protect Proinflammatory Cytokines Induced Beta Cell Apoptosis through the Ubiquitination
    Dong Mee Lim, Ju Young Kim, Kang Woo Lee, Keun Young Park, Byung Joon Kim
    Endocrinology and Metabolism.2011; 26(2): 142.     CrossRef
  • Exendin-4 Protects Oxidative Stress-Induced β-Cell Apoptosis through Reduced JNK and GSK3β Activity
    Ju-Young Kim, Dong-Mee Lim, Chan Il Moon, Kyung-Jin Jo, Seong-Kyu Lee, Haing-Woon Baik, Ki-Ho Lee, Kang-Woo Lee, Keun-Young Park, Byung-Joon Kim
    Journal of Korean Medical Science.2010; 25(11): 1626.     CrossRef
Letter
Original Articles
The Effect of Step-wised, Controlled Cooling Method for Islet Cryopreservation on the in vivo and in vitro Islet Function.
In Kyung Jeong, Seung Hoon Oh, Byung Joon Kim, Tae Young Yang, Byung Wan Lee, Chang Young Ha, Jung Hyung Noh, Jae Hoon Chung, Young Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim
Korean Diabetes J. 2002;26(1):65-74.   Published online February 1, 2002
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AbstractAbstract PDF
BACKGROUND
Although islet transplantation has been attempted to reverse the state of diabetes, achieving a critical number of islets and modulating the immune response limit the success ofl islet transplantation. Cryo-preservation of islets offers many important benefits for islet transplantation by collecting islets with a wide variety of HLA phenotypes and islet MHC expression. The aims of this study was to determine the optimal conditions for cryo-preservation by using a controlled cooling method and to evaluate in vitro and in vivo functional properties of the cryo-preserved islets. METHODS: Collagenase-isolated, Ficoll-purified islets were cultured for 48 hours. They were aliquoted into freezing tubes (1000 islets per tube), equilibrated with 2 M dimethyl sulfoxide (DMSO) in three steps, supercooled, nucleated, and controll- cooled at rate of 0.25 degrees C/min to - 40 degrees C prior to storage at - 196 degrees C. Rapid thawing and removal of DMSO with 0.75 M sucrose preceded 48 hour of culture and the morphology, viability, glucose-induced insulin secretion, and in vivo function of rats transplanted with cryopreserved islets was reexamined. RESULTS: 1) Recovery was 90.2+/-0.2%, 85.7+/-0.1% and 81.7+/-0.1% immediately after, 24 hours and 72 hours after thawing respectively. The viability was 60+/-5%, 80+/-5%, 90+/-5% immediately after, 24 hours and 72 hours after thawing respectively. 2) The glucose-stimulated-insulin secretion (GSIS) tended to decrease immediately after thawing, but GSIS increased to the level of pre-cryopreservation 72 hours after thawing. 3) The in dynamic GSIS, the first and the second phase of insulin secretion were well preserved in islets cultured for 72 hours after thawing. 4) The cryopreserved islets were cultured for 3 days and transplanted into renal sub-capsular space of streptozotocin (STZ) induced diabetic rats. The duration of normoglycemia in the STZ-induced diabetic rats transplanted with cryopreserved islets was significantly longer than that of the fresh islets. CONCLUSION: The optimal condition of cryopreservation using the controlled cooling method was established in rat pancreatic islets. This cryopreservation method can be a feasible approach for human islet transplantation.
Critical Factors Determined Islet Graft Function In Canine Islet Autotransplantation.
Tae Young Yang, In Kyung Jeong, Seung Hoon Oh, Sang Hoon Lee, Dong Jun Kim, Jong Ryul Hahm, Byung Joon Kim, Kyu Jeung Ahn, Sung Joo Kim, Jae Hoon Chung, Yong Ki Min, Myung Shik Lee, Moon Kyu Lee, Kwang Won Kim
Korean Diabetes J. 2000;24(2):170-179.   Published online January 1, 2001
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AbstractAbstract PDF
BACKGROUND
Islet cell transplantation is an attractive alternative to whole organ pancreas transplantation, since it is clearly safer and simpler surgical procedure for the reciplents. However, several obstacles still remain, because the free islets appear to be more susceptible to non-specific inflammatory damage or immune mediated destruction than islets in an intact pancreas. Therefore, the purpose of this study is to examine the functional outcome of islet autograft and the factors related to the islets graft survival in mongrel dogs. METHODS: Twelve adult mongrel dogs weighting 12~16 kg were used for the experiment of total pancratectomy and islet autotransplantation. The islets were properly isolated by a modified Recordi method. The obtained islets were further purified by centrifugation on discontinuous gradients using cell separation system (Model 2991, Cobe, Lakewood Colo). After the heparization(50U/kg), the islets were injected slowly into the liver through the portal vain for 30 minutes. The post-transplantation intravenous glucose tolerence test (IVGTT) with glucose disappearance rate (K), liver function test (LFT), fasting plasma glucose (FPG) ware measured periodically. RESULTS: I) The median of Ks were 1.3%/min (range 0.3~2.1) and the lEq/kg (150 m equivalents/kg of recipient body weight) was 3520 (range 1350-6550). The Ks in recipients with high lEq/kg (> or =5,000) were significantly higher than those in recipients with low lEq/kg (<5,000)(r=0.78, p<0.05). 2) The islet cell viability were estimated to be 95% and the median of the required insulin dosage for the maintenance of normal FPG were 0.7 (range 0~1.6) U/kg/day, The insulin requirement correlated well with the level of lEq/kg (r=-0.90, p<0.01). 3) The median of the volume of the transplanted pancreatic islet cell were 2.1 mL (range 0.7~5.0) and the purity was 60k (range 10~95), The portal pressure gradients of during the transplant procedure were 4.0(range 0.5~12.0) cmH20. The portal pressure gradients in recipients with high purity were significantly lower than those in recipients with low purity (r=-0,80, p<0,05). CONCLUSIONS: In this study, we confirmed that autotransplantation of islet cell on the pancreatectomized dogs can render nearly normoglycemia, and transplanted islet mass was most critical factor to successful autotransplantation in canine model.

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